Basic research on protein structure, function, regulation, and processes of folding/unfolding has produced the following results: (1) Heat-induced unfolding of dodecameric Mn~glutamine synthetase (Mn~GS) from E. coli at pH 7 has been studied by spectral techniques and by differential scanning calorimetry (DSC). In the absence of denaturant, cooperative interactions link partial, reversible unfolding reactions of all subunits within the GS dodecamer; mid-point T = 51.6 deg C. The enthalpy change for the latter is only 4% of that recently measured for the complete unfolding of GS (8 q 1 cal/g). (2) Thermal denaturation studies of the holo-tryptophan synthase (TS) complex (with bound pyridoxal phosphate (PLP)) from S. typhimurium show partial unfolding reactions are sequential. DSC and spectral data are consistent with a model of 6 sequential two-state transitions for holo-TS `~~` complex: 3 transitions at <65 deg C involve exposure of Trp177 and perturbation of bound PLP in ~ chains prior to unfolding of ` chains and 3 at >70 deg C occur as Tyr residues are exposed and ~ chains unfold. The cofactor increases both the linkage between unfolding domains and the stability of ~~ subunits. (3) Thermally induced partial unfolding reactions in Acanthamoeba myosin- II and intact rabbit skeletal muscle myosin have been characterized thermodynamically. Differences in the cooperative unfolding reactions of these myosins relate to differences in rod structures and possibly also head-rod interactions. ATP binding stabilizes head regions of both myosins. (4) Influenza virus hemagglutinin appears to adopt a molten globule conformation under fusogenic conditions (i.e., pH 4.9, 37 deg C). From pH 7.5 to 5.0, a destabilization of tertiary structures and a stabilization of secondary structures is evident. (5) Ultracentrifugation has been used to determine ligand promoted shape and size changes of macromolecules and also for studies of interacting biopolymers. Acanthamoeba myosin-II, E. coli ClpA and ClpP of the ATP- dependent protease complex, and glutamine synthetase were studied.